{PDOC51074} {PS51074; DPH_MB} {BEGIN} ********************************************** * DPH-type metal-binding (MB) domain profile * ********************************************** Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaebacteria to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyze the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death [1]. The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region which encodes a metal-binding (MB) domain. The DHP-type or CSL-type (named after the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity [2,3,4,5,6,7]. The DPH-type MB domain consists of a three-stranded beta-sandwich with one sheet comprising two parallel strands: (i) beta1 and (ii) beta6 and one anti- parallel strand: beta5. The second sheet in the beta-sandwich is comprised of strands beta2, beta3, and beta4 running anti-parallel to each other. The two beta-sheets are separated by a short stretch alpha-helix (see ) [4,6,7]. The profile we developed covers the whole DPH-type MB domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: July 2019 / Text revised. [ 1] Collier R.J. "Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century." Toxicon 39:1793-1803(2001). PubMed=11595641 [ 2] Liu S., Leppla S.H. "Retroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins." Mol. Cell 12:603-613(2003). PubMed=14527407 [ 3] Liu S., Milne G.T., Kuremsky J.G., Fink G.R., Leppla S.H. "Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2." Mol. Cell. Biol. 24:9487-9497(2004). PubMed=15485916; DOI=10.1128/MCB.24.21.9487-9497.2004 [ 4] Sun J., Zhang J., Wu F., Xu C., Li S., Zhao W., Wu Z., Wu J., Zhou C.-Z., Shi Y. "Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc-binding module." Biochemistry 44:8801-8809(2005). PubMed=15952786; DOI=10.1021/bi0504714 [ 5] Proudfoot M., Sanders S.A., Singer A., Zhang R., Brown G., Binkowski A., Xu L., Lukin J.A., Murzin A.G., Joachimiak A., Arrowsmith C.H., Edwards A.M., Savchenko A.V., Yakunin A.F. "Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain." J. Mol. Biol. 375:301-315(2008). PubMed=18021800; DOI=10.1016/j.jmb.2007.10.060 [ 6] Thakur A., Chitoor B., Goswami A.V., Pareek G., Atreya H.S., D'Silva P. "Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4." J. Biol. Chem. 287:13194-13205(2012). PubMed=22367199; DOI=10.1074/jbc.M112.339655 [ 7] Glatt S., Zabel R., Vonkova I., Kumar A., Netz D.J., Pierik A.J., Rybin V., Lill R., Gavin A.-C., Balbach J., Breunig K.D., Mueller C.W. "Structure of the Kti11/Kti13 heterodimer and its double role in modifications of tRNA and eukaryotic elongation factor 2." Structure 23:149-160(2015). PubMed=25543256; DOI=10.1016/j.str.2014.11.008 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}